NMR is a powerful technique for analyzing molecular structure. However it is also an insensitive technique compared to other techniques for structure determination. There has been a continued effort to increase the sensitivity. Prior efforts that have greatly increased the sensitivity of the technique comprise the use of Fourier Transform (U.S. Pat. No. 3,475,680), higher magnetic field strengths through the use of superconducting magnets, and the use of cooled and/or superconducting Radio Frequency (RF) receiving coils. Sensitivity can also be gained by lowering the sample temperature, to gain sample polarization. Most liquid samples freeze, forming a solid if the sample temperature is substantially lowered, yielding broad NMR lines that obscure the details of the NMR spectrum. The U.S. Pat. No. 6,515,260, assigned to the Assignee of the present invention, teaches polarizing the sample at a very low temperature and then melting the sample by quickly heating it to near room temperature. An NMR measurement is then performed before the sample has time to achieve thermal equilibrium at the higher temperature. Other methods of hyperpolarization, i.e. increasing the polarization of the sample above the polarization that could be obtained by thermal polarization alone include Dynamic Nuclear Polarization (DNP), Chemically Induced Nuclear Polarization (CIDNP) and Para-Hydrogen Induced Polarization. These last two methods can only be used to polarize selected molecules.
Ardenkjaer-Larson et al [Proceedings of the National Academy of Science volume 100, pages 10158–1063 (2003)] and J. Wolber et al [Nuclear Instruments and Methods in Physics Research A, Volume 526, pages 173–181 (2004)] have demonstrated an increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. The result was obtained by adding the analyte to a suitable solvent containing a free radical. The solution was then frozen and cooled to a temperature in the range of 1.5 Kelvin in a polarizing magnet with a magnetic field of 3.35 Tesla and allowed to achieve thermal equilibrium. (At this temperature the thermal polarization of a free radical is approximately 90%). A Dynamic Nuclear Polarization (DNP) technique was used to transfer a fraction of this electron polarization to one of the nuclear species in the analyte by irradiating the sample at a microwave frequency at or near the unpaired electron Larmor frequency, in this case at a frequency of approximately 94 GHz. This step transferred a fraction of the electron polarization to the nuclei in the sample. The sample was then quickly dissolved by mixing with additional unpolarized hot solvent thereby forming a liquid. The polarized liquid sample was then transferred to a standard HR NMR spectrometer where an enhanced NMR signal can be acquired. Unfortunately the experiment cannot be repeated using the same sample without additional processing to remove the excess solvent. The remaining paramagnetic ions in the sample also cause line broadening when acquiring the enhanced NMR signal.
There are a number of reports of generating high nuclear polarization in single crystals and polycrystalline material that have been doped with a photo-excited triplet-state forming molecule. Henstra et al (Chem. Phys. Lett., vol. 165, pages 6–10, 5 Jan. 1990) obtained a maximum enhancement of 5,500 of protons in a single crystal of naphthalene doped with pentacene, a photo-excited triplet state molecule. The experiment was carried out at room temperature. The triplet state was formed by irradiation of the crystal by a pulsed nitrogen laser. After the laser flash, the optically created electron spin polarization at sub-Kelvin spin temperature is transferred to the protons by applying a microwave pulse. The microwave pulse satisfies the Hartman-Hahn condition whereby the strength of the microwave field B1 satisfies the condition γeB1=γnB0, where γe and γn are the gyromagnetic ratios of the electron and the nucleus (is this case the proton) respectively. The integrated solid effect (ISE) was provided during the microwave pulse by sweeping the magnetic field through the nuclear line width. This process was repeated at a 25 Hz rate with an average laser power of about 70 mW. The pulsed microwave irradiation was applied starting 1 μs after each laser shot and had duration of 10 or 15 μs. The maximum proton polarization was obtained after 60 minutes of irradiation. Other similar experiments have been carried out on single crystal or polycrystalline solid materials. This and similar experiments produce high nuclear polarization of single crystal or polycrystalline molecules that form a triplet states molecules when photo-irradiated, however it does not enable the production of high polarization in liquid state molecules, or samples dissolved in liquid solvents as used in high resolution NMR experiments.